Synthesis of 2-chloro-6-fluoro quinoline-3-carbaldehyde (4)

N,N-dimethylformamide (29.9 mL) was added to a 100 mL round-bottom flask guarded with drying tube; it was cooled to 0 °C using ice bath. Then, phosphorus oxychloride (84.3 mL) was added dropwise to it from dropping funnel guarded by drying tube while being stirred by magnetic stirrer. This addition was done for 30 min. Then N-(4-flouro phenyl) acetamide (19.69 g, 0.00012 mmol) was added to it after 5 min. The dropper funnel was replaced by air condenser with guarding tube at its end and the mixture was heated for 22 h on oil bath at 85–90 °C. Then it was cooled to room temperature, poured into a beaker containing 400 mL crushed ice water, and stirred for 20 min. The yellow solid product was collected by suction filtration and washed with 100 mL cold water. The crude yield was 16.4 g (60.8%) and was recrystallized from ethyl acetate. yellow crystal; mp 160^_162 °C; yield 15.5 g (57.5%); R_f 0.72 (n-hexane:EtOAc, 4:1); ¹H NMR (400 MHz, CDCl₃): δ 9.36 (1H, s, H-9), 7.54 (1H, s, H-4), 6.85 (1H, dd, J = 12.8 Hz and 3.2 Hz, H-7), 6.47 (1H, d, J = 12 Hz, H-8), 6.32 (1H, d, J = 8.4 Hz, H-5); ¹³C NMR (101 MHz, CDCl₃): δ 189.1 (C-9), 162.2 (C-6), 148.6 (C-2), 143.9 (C-8a), 139.7 (C-4), 130.77 (C-8), 130.0(C-4a), 127.6 (C-3), 123.8 (C-7), 111.2 (C-5).